Social defeat stress induces hyperalgesia and increases truncated BDNF isoforms in the nucleus accumbens regardless of the depressive‐like behavior induction in mice

Abstract

Epidemiological studies have shown a close association between pain and depression. There is evidence showing this association as patients with depression show a high chronic pain prevalence and vice versa. Considering that social stress is critical for the development of depression in humans, we used a social defeat stress (SDS) model which induces depressive-like behavior in mice. In this model, mice are exposed to an aggressor mouse for ten days, suffering brief periods of agonistic contact and long periods of sensory contact. Some mice display social avoidance, a depressive-like behavior, and are considered susceptible, while some mice do not, and are considered resilient. Thus, we investigated the nociceptive behavior of mice submitted to SDS and the neuroplastic changes in dopaminergic mesolimbic system. Our results showed that the stressed mice (resilient and susceptible) presented a higher sensitivity to pain than the control mice in chemical and mechanical tests. We also verified that susceptible mice have higher Bdnf mRNA in the VTA compared to the resilient and control mice. The stressed mice had less mature BDNF and more truncated BDNF protein in the NAc compared with control mice. Although social stress may trigger the development of depression and hyperalgesia, these two conditions may manifest independently as social stress induced hyperalgesia even in mice that did not display depressive-like behavior. Also, increased Bdnf in the VTA seems to be associated with depressive-like behavior, whereas high levels of truncated BDNF and low mature BDNF appear to be associated with hyperalgesia induced by social defeat stress.

Social Defeat Stress (SDS) in Mice: Using Swiss Mice as Resident

“…www.bio-protocol.org/e3197 Bio-protocol 9(06): e3197. DOI:10.21769/BioProtoc.3197 (Pagliusi et al, 2018) as well as all the behavioral results presented here. We are extremely grateful for the previous studies carried out by Golden et al (2011) which allowed us to be able to replicate the social defeat stress model even with modifications.…”

“…After this period a relationship of social submission is characterized, typically observed in human relations. As a result, stressed mice develop several physiological and behavioral changes, including altered levels of corticosterone, cardiac hypertrophy, circadian rhythm disturbances, widespread pain, anxiety, despair behavior, anhedonia and social avoidance ( Krishnan et al , 2007 ; Pagliusi et al , 2018 ). Social interaction level is used to assess depressive-like behavior and, interestingly, some mice submitted to this social defeat stress protocol are resistant and do not develop social avoidance, similar to what occurs in humans, where not all individuals exposed to some form of chronic social stress develops psychopathologies ( Krishnan et al , 2007 ).…”

“…We are grateful to São Paulo Research Foundation (FAPESP) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) for funding the study of the original article ( Pagliusi et al , 2018 ) as well as all the behavioral results presented here. We are extremely grateful for the previous studies carried out by Golden et al (2011) which allowed us to be able to replicate the social defeat stress model even with modifications.…”

Pathogenesis of Fibromyalgia in Patients With Autoimmune Diseases: Scoping Review for Hypothesis Generation

“…The chronic stress can both increase central sympathetic outflow and alter the immune response of the individual. It has been shown in animal models that chronic stress in the form of social defeat increases the susceptibility to pain and hyperalgesia [38,39].…”

Intra‐accumbal dopaminergic system modulates the restraint stress‐induced antinociceptive behaviours in persistent inflammatory pain

“…Stress‐induced analgesia is influenced by age, gender and prior experience with stressful conditions (Butler & Finn, 2009). Stress and pain are two complicated phenomena with a complex relationship where pain can cause stress (Sieberg et al., 2018); stress may increase or decrease pain (Heidari‐Oranjaghi et al., 2012; Pagliusi Jr et al, 2018; Shamsizadeh et al., 2014). It appears that acute stress can produce analgesia in animals and humans, while repetitive stress seems to favour the induction of hyperalgesia in rodents (Bardin et al., 2009).…”